title: Single-dose fosaprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with cisplatin therapy: randomized, double-blind study protocol--EASE.
abstract: OBJECTIVE
  Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant.
  
  
  METHODS
  A randomized, double-blind, active-control design was used to test whether fosaprepitant is noninferior to aprepitant. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points.
  
  
  RESULTS
  A total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively).
  
  
  CONCLUSIONS
  Given with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.
authors.affiliation: University of Vermont, Dept of Medicine, Fletcher Allen Health Care, 89 Beaumont Ave, Given Bldg E-214, Burlington, VT 05405, USA. steven.grunberg@uvm.edu
authors.forename: Steven
authors.initials: S
authors.lastname: Grunberg
authors.forename: Daniel
authors.initials: D
authors.lastname: Chua
authors.forename: Anish
authors.initials: A
authors.lastname: Maru
authors.forename: José
authors.initials: J
authors.lastname: Dinis
authors.forename: Suzanne
authors.initials: S
authors.lastname: DeVandry
authors.forename: Judith A
authors.initials: JA
authors.lastname: Boice
authors.forename: James S
authors.initials: JS
authors.lastname: Hardwick
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Beckford
authors.forename: Arlene
authors.initials: A
authors.lastname: Taylor
authors.forename: Alexandra
authors.initials: A
authors.lastname: Carides
authors.forename: Fausto
authors.initials: F
authors.lastname: Roila
authors.forename: Jørn
authors.initials: J
authors.lastname: Herrstedt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000077608:Aprepitant; D002945:Cisplatin / Q000009:adverse effects*; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced* / Q000517:prevention & control*; D017294:Ondansetron / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced* / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D009025:Morpholines; D000077608:Aprepitant; D017294:Ondansetron; C579707:fosaprepitant; D003907:Dexamethasone; D002945:Cisplatin